Adult male rats receiving a single i.p. injection of kepone (80 mg/kg) exhibit tremors within a few hours after the injection. Since kepone-elicited tremors are relieved by injections of muscarinic receptor blockers, we measured acetylcholine turnover in various brain structures. We failed to detect evidence for an involvement of cholinergic presynaptic mechanisms in kepone toxicity. Kepone inhibits the turnover rate of GABA in striatum. Moreover, we found that kepone down-regulated 5HT1 receptors and increased the turnover of serotonin in hippocampus and striatum. These results suggest the possibility that kepone decreased GABAergic tone indirectly by an increase of serotonergic firing thereby increase cholinergic tone in striatum, causing tremors.